The epidemic growth factor receptor (EGFR) is a member of the family of epidemic growth factor genes (erbB), which is overexpressed in about 30% of human tumors, especially non-small cell lung carcinomas, head and neck squamous cell carcinomas, colorectal carcinomas and the like. Many studies indicate that antibodies against EGFR may effectively inhibit EGFR signal transduction pathway by blocking the binding of ligands extracellularly, which showed promising therapeutic effect on multiple EGFR overexpressing or mutated human tumors, especially head and neck squamous cell carcinomas (80%˜100%), colorectal cancer (25%˜77%), non-small cell lung cancer (40%˜80%) and the like. Epidemic growth factor receptor is one of the current therapeutic targets for tumor that are intensively investigated and well-focused at present. Utilizing genetic engineering in developing an anti-EGFR monoclonal antibody becomes one of research hotspots for immunotherapy of tumor.
In 2004 and 2006, the U.S. Food and Drug Administration had successively approved a murine-human chimeric antibody cetuximab and a full human antibody panitumumab against EGFR for treatment of colorectal carcinomas; in 2005, a humanized antibody nimotuzumab against EGFR was awarded new drug certificate by Chinese State Food and Drug Administration (SFDA), its Phase II/III clinical trial is under way. Use of murine monoclonal antibody in human bodies may induce human anti-murine antibody reaction, and thereby affecting its functions thereof. Application of genetic engineered murine-human chimeric antibody can greatly reduce the immunogenicity of the murine monoclonal antibody, prolong the half life of the antibody in bodies, and further enhance the biological effect of the antibody by virtue of the Fc region of human immunoglobulin mediated immunomodulation and ADCC effect; however, the ability of this chimeric antibody to bind to an antigen is lower than that of the murine antibody by 98.7%. A large number of pre-clinical trials and clinical trials each has proven that cetuximab, alone and in combination with chemotherapy/radiotherapy, has a better therapeutic effect, but simple CDR transplant tends to cause drop in antigen-antibody affinity; panitumumab is a full human antibody prepared with transgenic mice technology, which, comparing with the chimeric antibody and humanized antibody, has a human sequence of near 100%, greatly increasing the antibody-target affinity, but this antibody has such defects as glycosylation pattern of murine, short half life, more hypersensitivity reactions and the like. Nimotuzumab gives a humanized antibody through humanized remodeling of the anti EGFR murine monoclonal antibody, which links the light and heavy chains of the antibody respectively to different expression vectors for expression; since the expressions of the light and heavy chains are quite different, the molecular expression level of the complete antibody tends to be very low.